High dose exposure of animals to methamphetamine [MA] causes significant damage to frontostriatal brain regions, which are relatively rich in dopaminergic [DA] and serotonergic [5-HT] innervation. Although animal models of drug addiction are extremely valuable, convergent findings from human studies are critical if one is to understand the impact of long-term MA use on the human brain. The goal of this proposal is to examine the effects of long-term effects of MA use in frontostriatal regions using proton magnetic resonance spectroscopy [MRS] in conjunction with mature neurons (primarily N- acetyl aspartase [NAA], high energy metabolic products (phosphocreatine and creatine [Cr], cell membrane synthesis or degradation (choline [Cho]), and glia (myoInositol [mI). MRS is a safe non-invasive tool that can detect certain proton spectroscopic metabolite patterns associated with brain damage and has been validated as a viable tool in detecting neuronal damage in both animals and humans. The interdisciplinary approach of MRS and cognitive assessment will yield valuable data essential for understanding the cognitive sequelae of neuronal damage resulting from MA abuse. Our preliminary data from methamphetamine dependent (MD) subjects (n=9) reveal likely neuronal damage in the prefrontal cortex [PFC] and anterior cingulate [ACC] as well as deficits on attentional tasks subserved by these regions. The proposed work is essential to confirm these clinically important findings by testing a larger sample of MD subjects and controls, using MRS in conjunction with sensitive computerized tasks of attention and memory. NAA, Choline, myo- Inositol and creatine will be measured in the PFC (dorsal and ventral), ACC, striatum, and control structures (primary visual cortex). Group differences in levels of NAA, Chol, mI, and Cr in the above regions will be determined by repeated measured analysis of variance. A similar analysis approach will be applied to the behavioral data. Correlational analyses between cognitive measures and imaging data from specific hypothesized regions of interest will be conducted.